Abstract 17002: Post-Arrest Arterial Hyper-Oxygenation and Cardiac Mitochondrial Function

Abstract

Introduction: Post-ischemic re-oxygenation is necessary to minimize ischemic injury, but itself can induce further reperfusion injury through the induction of reactive oxygen species (ROS). Utilization of oxygen within the cell primarily occurs in the mitochondria. The objective of this study was to determine heart mitochondrial function following 1 hour of controlled arterial oxygenation following cardiac arrest and ROSC. We hypothesized that arterial hyper-oxygenation following ROSC would result in greater impairment of heart mitochondrial function. Methods: Two experimental protocols were completed using a rat KCl arrest model. In experiment 1, animals underwent a 6 min cardiac arrest and were resuscitated with standard thumper CPR, ventilation and epinephrine and then ventilated with 100% O2 (hyperoxia group) or 40% O2 (normoxia group) for 60 min. In experiment 2, animals underwent a 25 min cardiac arrest and were resuscitated with cardiopulmonary bypass. Arterial PO2 was titrated to either hyperoxic or normoxic levels for 60 min post ROSC. In both experiments, at the end of 60 min, heart mitochondria were isolated and mitochondrial respiratory function was compared between groups. Results: In experiment 1, post-ROSC arterial PaO2 was 280 ± 40 mm Hg in the hyperoxic group and 105 ± 10 mm Hg in the normoxic group. Mitochondrial respiration, defined as respiration control ratio (state 3/4 respiration), was significantly higher in the normoxic group compared to the hyperoxic group (n=6/group, p <0.05). In experiment 2, during the 60 min post ROSC period, arterial PaO2 was 441 ± 10 mm Hg in the hyperoxic group and 107 ± 9 mm Hg in the normoxic group (n=6/group, p<0.001). Mitochondrial respiration, 60 min after ROSC, was significantly higher in the hyperoxic group compared with the normoxic group (n=6/group, p<0.05). Post-ROSC arterial hyperoxemia (compared with normoxemia) was associated with worse mitochondrial function after a short cardiac arrest but improved mitochondrial function after a prolonged cardiac arrest. We conclude that post-ischemic arterial hyperoxia is an important variable in mitochondrial functional recovery but the severity of the ischemia may attenuate this effect by limiting reperfusion oxygen delivery to the mitochondria.